Calcium and Bone Metabolism: Implications for EB

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Calcium and Bone MetabolismImplications for EB

• Anna L. Bruckner, MD
• Stanford University School of Medicine

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Overview

• What leads to strong bones in normal individuals?
• What is known about bone health in EB?
• Why are bones at risk in EB?
• What can we do about it?

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Bones are like a bank

• Deposits into the savings account of bone
  density are made in childhood, adolescence, and
  early adulthood
• Withdrawals are made after middle age
• Building an adequate reserve by early adulthood
  is critical

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Changes in bone mass over time
Davies JH et al. Arch Dis Child 200590373-378.
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Goals of bone health

• An ounce of prevention is worth a pound of cure
• Optimize gains in bone mass
• Minimize losses
• Prevent fractures

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Bone health the players

• Heredity
• Many gene polymorphisms can affect bone mass
• Nutrition
• Physical activity
• Hormonal factors
• Modifiable factors

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Nutrition Adequate calories

• Nutritional inadequacy predisposes to osteopenia
• Adolescents with anorexia nervosa
• Overweight children also likely to have reduced
  bone mineral density and increased fracture risk

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NutritionCalcium

• Contributes to accruing bone mass
• Anabolic effect on growing skeleton
• Helps prevent subsequent bone loss

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Recommended Calcium Intake

• Age (years)
• 1-3
• 4-8
• 9-18
• 19-50
• 51
• TOO Much
  

• Milligrams / day
• 500
• 800
• 1300
• 1000
• 1200
• gt2500

National Academy of Science, 1997
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Sources of calcium

• Milk / dairy products
• Calcium fortified orange juice
• Tofu / soy milk
• Beans
• Dark green leafy vegetables
• Calcium supplements

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Have a Coke and a fracture?

• Soft drink consumption associated with fractures
  in girls
• Due to displacement of milk from diet

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Nutrition Vitamin D

• Necessary for bone mineralization
• Primary source is skin
• Vitamin D precursors added to milk (in U.S.)
• Serum 25 OH-Vit D reflects stores

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Vitamin D Supplementation

• 200 I.U. recommended daily for
• Infants taking lt 500 ml/d vitamin D-fortified
  milk or formula
• Children adolescents who
• Do not get regular sun exposure
• Consume lt500 ml/d vitamin-D fortified milk
• Gartner LM and Greer FR. Pediatrics 2003111
  908-910.

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Physical activity

• Weight-bearing activity is necessary to maintain
  and increase bone mass
• Immobility leads to bone loss

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Mechanostat theory
Bachrach LK. Trends Endocrinol Metab 20011222-8.
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Hormonal status

• Adequate thyroid hormone, growth hormone, IGFs,
  sex steroids needed
• GH acts on bones via IGF-1
• Anabolic effects of sex hormones
• Estrogen modulates bone remodeling

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Bones and EB

• Bones appear thin on plain films
• Wong WL and Pemberton J. Br J Radiol 1992
  Jun65480-4.
• One reported case of 25-yr-old with RDEB and
  osteoporosis treated with calcium and vit D
• Kawaguchi M et al. Br J Dermatol 1999141934.

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Bones and EB, cont.

• Study of 7 patients with RDEB, JEB-nH
• 3-8 years old
• Variables
• Nutritional intake
• Physical activity
• Height, BMI
• Bone mineral density
• Biochemical markers (e.g. 25 OH-Vit D)

Reyes ML et al. J Pediatr 2002140467-9.
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Results

• Caloric, calcium intake normal
• Moderate limitation on activity in 4 severe in 2
• Decreased bone mineral density (BMD) in 3
• Reyes ML et al. J Pediatr 2002140467-9.

Patients with lowest BMD had low 25-OH Vit D
levels and severe limitations on activity
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How EB impacts bones

• Nutritional adequacy
• Increased caloric needs
• Malnutrition / undernutrition
• Restricted intake
• Decreased absorption
• Undernutrition affects hormone levels reduced
  IGF-1 expression, GH resistance, hypogonadism

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How EB impacts bones, cont.

• Calcium
• Adequate amount needed for EB patients unclear

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How EB impacts bones, cont.

• Vitamin D
• Less skin exposure to sunlight due to extensive
  bandaging, limited outdoor exposure
• Caloric supplements may not be Vit D fortified

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How EB impacts bones, cont.

• Inactivity
• Pain from blistering and joint contractures
  limits weight-bearing activities

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How EB impacts bones, cont.

• Does the chronic inflammation associated with
  wound healing impact bone mineralization?
• Certain medications (e.g. corticosteroids)
  negatively affect bone density

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Changes in bone mass over time
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Optimizing bone health in EB

• Ensure adequate caloric intake
• Closely follow height and weight
• Ensure adequate intake of calcium
• Discourage soft drinks
• Vitamin D supplementation

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Optimizing bone health in EB

• Encourage weight-bearing activity
• Adequate padding of feet to minimize blistering
• Physical therapy to maintain joint mobility
• Are there other ways to optimize bone loading in
  a way that is not traumatic to the skin?

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Measuring bone density

• Dual-energy x-ray absorptiometry (DXA) preferred
  method

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DXA

• Few practice guidelines for pediatric patients
• Use clinical judgment based on disease severity
  and other risks
• Indications
• Bone pain
• Fracture after minimal trauma / recurrent
  low-impact fractures
• Osteopenia on plain films

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DXA, cont.

• Pediatric pitfalls in interpreting report
• Z scores (not T scores) are needed for patients
  lt 20 years old
• No standardized norms for pediatric BMD
• BMD based on pubertal stage or bone age may be
  more appropriate

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DXA, cont.

• How will we use BMD information in practice?
• Low BMD ? osteoporosis
• Osteoporosis low BMD, bone deterioration,
  increased fracture risk
• Fracture threshold in pediatric (and EB) patients
  unclear

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Bisphosphonates

• No published data on use in EB
• Pediatric bone experts recommend them for
• Osteogenesis imperfecta
• Children with fragility fractures
• Randomized controlled trials
• NOT low bone density alone

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In closing

• Need more studies about bone health in EB
  patients
• Need to determine optimal approach to preventing
  and treating low BMD in EB

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Acknowledgment

• Laura Bachrach, MD, Professor of Pediatrics,
  Division of Pediatric Endocrinology, Stanford
  University School of Medicine

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References

• Bachrach LK. Trends Endocrinol Metab
  20011222-8.
• Bachrach LK. Endocrinol Metab Clin N Am
  200534521-35.
• Davies JH et al. Arch Dis Child 200590373-8.
• Gartner LM and Greer FR. Pediatrics 2003111
  908-910.
• Kawaguchi M et al. Br J Dermatol 1999141934.
• Lanou AJ et al. Pediatrics 2005115736-43.
• Reyes ML et al. J Pediatr 2002140467-9.
• Wong WL and Pemberton J. Br J Radiol
  199265480-4.
• Zacharin M. Curr Opin Pediatr 200416545-51.